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- Title
CLHM-1 is a Functionally Conserved and Conditionally Toxic Ca<sup>2+</sup>-Permeable Ion Channel in Caenorhabditis elegans.
- Authors
Tanis, Jessica E.; Zhongming Ma; Krajacic, Predrag; Liping He; Foskett, J. Kevin; Lamitina, Todd
- Abstract
Disruption of neuronal Ca2+ homeostasis contributes to neurodegenerative diseases through mechanisms that are not fully understood. A polymorphism in CALHM1, a recently described ion channel that regulates intracellular Ca2+ levels, is a possible risk factor for late-onset Alzheimer's disease. Since there are six potentially redundant CALHM family members in humans, the physiological and pathophysiological consequences of CALHM 1 function in vivo remain unclear. The nematode Caenorhabditis elegans expresses a single CALHM1 homolog, CLHM-1. Here we find that CLHM-1 is expressed at the plasma membrane of sensory neurons and muscles. Like human CALHM1, C. elegans CLHM-1 is a Ca2+ -permeable ion channel regulated by voltage and extracellular Ca2+ . Loss of clhm-1 in the body-wall muscles disrupts locomotory kinematics and biomechanics, demonstrating that CLHM-1 has a physiologically significant role in vivo. The motility defects observed in clhm-1 mutant animals can be rescued by muscle-specific expression of either C. elegans CLHM-1 or human CALHM1, suggesting that the function of these proteins is conserved in vivo. Overexpression of either C. elegans CLHM-1 or human CALHM 1 in neurons is toxic, causing degeneration through a necrotic-like mechanism that is partially Ca2+ dependent. Our data show that CLHM-1 is a functionally conserved ion channel that plays an important but potentially toxic role in excitable cell function.
- Subjects
HOMEOSTASIS; NEURODEGENERATION; SENSORY neurons; EXTRACELLULAR matrix; BIOMECHANICS
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 30, p12275
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5919-12.2013